Growth, puberty, and endocrine functions in patients with sporadic or familial neurofibromatosis type 1: a longitudinal study.
ABSTRACT This study prospectively evaluates parameters of growth, puberty, and attained adult height in children with sporadic or familial occurrence of neurofibromatosis type 1 (NF-1), followed up longitudinally, to define the most important factors affecting these parameters.
The study was made up of 89 patients (55 boys, 34 girls) with sporadic (n = 45) or familial NF-1 (13 affected fathers and 31 affected mothers). The average age at referral was 8.9 years (range 8.5-15 years), and the average follow-up period was 8.5 years (6-15 years). A total of 28 patients attained adult height at the time of the report. Anthropometric measurements and bone age determinations were performed at 6- to 12-month intervals. As indicated, central nervous system (CNS) imaging was performed on 60 patients. Serum levels of thyroid stimulating hormone, free T4, lutheinizing hormone, follicle stimulating hormone, testosterone or estradiol, cortisol, and prolactin were measured in all patients periodically, and the pituitary growth hormone reserve was assessed in 32 short patients.
CNS pathology was found in 23 of the 89 patients. A total of 6 patients required neurosurgery, and 2 patients had cranial irradiation. Of these patients, 3 were receiving recombinant growth hormone and thyroxin replacement therapy and 5 patients with precocious puberty were treated with a gonadotropin-releasing hormone analog. All other patients had normal endocrine tests. Precocious puberty was recorded in 5 patients and was more common among the familial cases. The 5 patients with precocious puberty also had CNS pathology. Short stature (<10th percentile) was observed in 25.5% of the patients during the prepubertal period with a significant gradual reduction of their relative height for age (standard scores) during puberty. Short adult height was noted in 12 (43%) of 28 patients, and only 50% of the 28 patients attained an adult height that was appropriate for their respective target height. Short stature was more common among patients with familial NF-1, particularly if the father was affected, and among those patients with CNS pathology. Parental short stature was observed in 39% of the mothers and in 33% of the fathers (59% and 54% among the affected parents, respectively). Tall stature (>90th percentile) was observed in 4 of 89 patients (4.5%), who all had CNS tumors. A highly significant correlation was found among all adult height-predicting parameters (r =.79), and attained adult height was best correlated with the target height (r =.7; n = 28).
Short adult height is an important characteristic of NF-1 and deserves to be emphasized in the evaluation and follow-up of these patients during childhood. Short adult height is strongly linked with familial background of NF-1, in particular if the affected parent is the father, and is affected adversely by the relatively poor pubertal growth. Despite normal pituitary gland and thyroid function tests in most children and adolescents with NF-1, increased incidence of precocious puberty was observed. As the clinical expression in the second generation is more pronounced, the underlying mechanism seems to be mediated by genetic factors that are yet undefined.
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ABSTRACT: Neurofibromatosis 1 is a complex inherited neurocutaneous disease that is often difficult to diagnose early because of its age-dependent presentation. The diagnosis is also extremely difficult to communicate to patients and their parents because of the disease's clinical variability, unpredictable evolution, and uncertain prognosis. Since 1988, the year of publication of the last Consensus Conference statement concerning the diagnosis of neurofibromatosis 1, our understanding of the disease has naturally increased and, in addition to the availability of increasingly precise molecular analyses, some new clinical signs have been reported such as anaemic nevi, unidentified bright objects, choroidal hamartomas, and a typical neuropsychological phenotype. We critically review the current diagnostic criteria, and suggest the addition of new signs on the basis of published findings and our own clinical experience. This proposal aims to improve diagnostic power in paediatric age, securing a better and more reliable healthcare transition toward adult age. We finally recommend a new Consensus Conference in order to revise the diagnostic criteria, possibly differentiated by age of presentation.European Journal of Internal Medicine 07/2014; 25(6). DOI:10.1016/j.ejim.2014.04.004 · 2.30 Impact Factor
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ABSTRACT: We report the case of a 31 year-old male from Cajamarca, Peru, with cognitive problems since childhood, who at 12 year-old developed increased volume and deformation of his right lower limb and to a lesser extent of his left, associated to massive skin folding, growth of subcutaneous nodules, elephantine look due to nerve cords formation in thigh and leg, pain and functional walking limitation. Concomitantly generalized skin café au lait spots, subcutaneous nodules, and Lisch nodules in both irides. Magnetic resonance and contrast TAC revealed abundant uniform plexiform nodules in abdomino-pelvic cavity forming masses and cords that continued throughout his thigh as lumps and cords. In addition, the patient presented bone dysplasia (thinning of femur and tibia cortex, pseudoarthrosis, new left cotyle formation). Contrast magnetic resonance showed triventricular normotensive hydrocephalus.09/2009; 70(3):205-210.
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ABSTRACT: Die Neurofibromatose Typ 1 (NF1) ist eine häufige, autosomal-dominant erbliche Phakomatose. Die Diagnostik, basierend auf den NIH- (,,National Institutes of Health-“) Kriterien, führt oftmals im Kindesalter zu einer verzögerten Krankheitserkennung.Deutschlandweit wurden 102 NF1-Patienten (im Mittel 10,8 Jahre alt) untersucht. Neben den NIH-Diagnosekriterien wurden die erste Dentition, Körpergewicht, Körpergröße und Kopfumfang von der U1 bis U9 dokumentiert und einem Kontrollkollektiv von 51 gesunden Geschwistern sowie einer Gruppe gesunder, nicht verwandter Kinder gegenübergestellt.Der Anteil der Frühzahner war mit 31% unter den NF1-Patienten im Vergleich zu gesunden Geschwistern erhöht (8,9%). Körpergröße und Körpergewicht der NF1-Patienten unterschieden sich in den ersten 5 Lebensjahren nicht signifikant von gleichaltrigen gesunden Kindern. Jedoch hatten NF1-Patienten ab dem vollendeten 1. Jahr einen signifikant größeren Kopfumfang.Der hohe Anteil an Frühzahnern und der größere Kopfumfang ab dem vollendeten 1. Lebensjahr können den Verdacht auf das Vorliegen einer NF1 verstärken. Die Diagnostik in den ersten 5 Lebensjahren sollte deshalb vor allem bei Kindern auf Verdacht einer Neumutation auch Nebensymptome wie Makrozephalus und eine verfrühte Dentition umfassen.Monatsschrift Kinderheilkunde 01/2008; 156(9). · 0.28 Impact Factor